Cellular and Molecular Life Sciences

, Volume 67, Issue 10, pp 1567–1579

Tumor necrosis factor-mediated cell death: to break or to burst, that’s the question

Authors

  • Franky Van Herreweghe
    • Unit For Molecular Signalling and Cell Death, Department for Molecular Biomedical ResearchVIB
    • Unit for Molecular Signalling and Cell Death, Department of Biomedical Molecular BiologyGhent University
  • Nele Festjens
    • Unit for Molecular Glycobiology, Department for Molecular Biomedical Research, VIBGhent University
    • Laboratory for Protein Biochemistry and Biomolecular Engineering, Department of Biochemistry and MicrobiologyGhent University
  • Wim Declercq
    • Unit For Molecular Signalling and Cell Death, Department for Molecular Biomedical ResearchVIB
    • Unit for Molecular Signalling and Cell Death, Department of Biomedical Molecular BiologyGhent University
    • Unit For Molecular Signalling and Cell Death, Department for Molecular Biomedical ResearchVIB
    • Unit for Molecular Signalling and Cell Death, Department of Biomedical Molecular BiologyGhent University
Multi-author Review

DOI: 10.1007/s00018-010-0283-0

Cite this article as:
Van Herreweghe, F., Festjens, N., Declercq, W. et al. Cell. Mol. Life Sci. (2010) 67: 1567. doi:10.1007/s00018-010-0283-0

Abstract

In this review, we discuss the signal-transduction pathways of three major cellular responses induced by tumor necrosis factor (TNF): cell survival through NF-κB activation, apoptosis, and necrosis. Recruitment and activation of caspases plays a crucial role in the initiation and execution of TNF-induced apoptosis. However, experimental inhibition of caspases reveals an alternative cell death pathway, namely necrosis, also called necroptosis, suggesting that caspases actively suppress the latter outcome. TNF-induced necrotic cell death crucially depends on the kinase activity of receptor interacting protein serine-threonine kinase 1 (RIP1) and RIP3. It was recently demonstrated that ubiquitination of RIP1 determines whether it will function as a pro-survival or pro-cell death molecule. Deeper insight into the mechanisms that control the molecular switches between cell survival and cell death will help us to understand why TNF can exert so many different biological functions in the etiology and pathogenesis of human diseases.

Keywords

Tumor necrosis factorApoptosisNecrosisReceptor interacting protein kinase 1

Copyright information

© Springer Basel AG 2010